CN101879272A - Chinese medicinal compound for treating coronary heart diseases, preparation method and application thereof - Google Patents

Chinese medicinal compound for treating coronary heart diseases, preparation method and application thereof Download PDF

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CN101879272A
CN101879272A CN 201010211975 CN201010211975A CN101879272A CN 101879272 A CN101879272 A CN 101879272A CN 201010211975 CN201010211975 CN 201010211975 CN 201010211975 A CN201010211975 A CN 201010211975A CN 101879272 A CN101879272 A CN 101879272A
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chinese medicine
coronary heart
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CN101879272B (en
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严冬
钱玉良
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Nanjing University of Chinese Medicine
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Nanjing University of Chinese Medicine
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Abstract

The invention discloses a Chinese medicinal compound for treating coronary heart diseases, a preparation method and application thereof. The Chinese medicinal compound consists of the following raw materials in part by weight: 6 to 60 parts of dwarf lilyturf tuber, 3 to 15 parts of common macrocarpium fruit, 3 to 20 parts of leech, 6 to 60 parts of rhodiola rosea, 6 to 60 parts of ginkgo leaf and 6 to 60 parts of giant knotweed rhizome. The Chinese medicinal compound provided by the invention is prepared in proportion by adopting the theory of syndrome differentiation and treatment according to the theory of the traditional Chinese medical science, pharmacological experimental results indicate that the Chinese medicinal compound provided by the invention has the excellent effects of nourishing heart and kidney, clearing heat and invigorating blood circulation and eliminating blood stasis and removing obstruction in channels, and the modern pharmacological study indicates that the Chinese medicinal compound has the strong effects of improving myocardial oxygen-carrying capacity, expanding the coronary artery, anticoagulating, resisting inflammation, reducing lipid and the like, so the Chinese medicinal compound can resist myocardial ischemia, relieve angina of the coronary heart diseases, resist arteriosclerosis and prevent thrombosis; and the Chinese medicinal compound provided by the invention has low adverse reactions and can be used for treating the coronary heart diseases.

Description

A kind of Chinese medicine compound for the treatment of coronary heart disease and preparation method thereof and application
Technical field
The present invention relates to a kind of Chinese medicine compound, be specifically related to a kind of Chinese medicine compound, the invention still further relates to the application of this Chinese medicine compound in preparation treatment coronary heart disease with the effect of treatment coronary heart disease.
Background technology
Cardiovascular disease has become one of principal disease of harm humans health, cause death cases in rising trend because of cardiovascular disease every year, wherein coronary heart disease is the commonly encountered diseases in the cardiovascular disease, coronary heart disease is with the urgency of falling ill, the mortality rate height, refractory more is characteristics of incidence, has more medicine at coronary heart disease at present, especially based on chemical drugs, with expansion hat medicine, as nitroglycerin class medicine, anticoagulant, platelet aggregation inhibitor is main, and these medicines have been obtained curative effect preferably clinically, can alleviate patient's misery, but most medicines can only of short durationly improve the coronary ischemia symptom, and the state of an illness recurs easily, and takes for a long time, side effect is big, and can not fundamentally improve the coronary ischemia symptom.Chinese medicine has special advantages aspect the treatment coronary heart disease, can not only effectively improve the coronary ischemia symptom, and the length of holding time, untoward reaction is little, little to patient's organ injury, as Chinese invention patent 01108286.0,200410018357.9,03152897.X 200310103981.4,02114549.0 grades all disclose the medicine of treatment coronary heart disease, but it is more that the inclined to one side QI invigorating warming YANG of existing Chinese medicine preparation is invigorated blood circulation, rarely have the Chinese medicine preparation with the cloudy double heat clearing away of invigorating blood circulation of invigorating heart and kidney gas, can not adapt to the new needs that change of current incidence of coronary heart disease, clinical syndrome differentiation selects medicine leeway little.Therefore, it is obvious to develop a kind of curative effect, and dosage is few, meets clinical needs, medicaments for coronary disease is significant safely and effectively.
Summary of the invention
Goal of the invention: the objective of the invention is to solve the deficiencies in the prior art, provide a kind of proportioning scientific and reasonable, have nourishing heart-disney, heat clearing and blood circulation promoting, the disperse blood stasis and dredge collateral effect can obviously improve coronary circulation, improves myocardial ischemia, has antianginal, antithrombotic, anticoagulant, antiinflammatory, improve the Chinese medicine compound of lipid metabolism effect, another object of the present invention provides the application of this Chinese medicine compound in preparation treatment medicaments for coronary disease.
Technical scheme: in order to realize above purpose, the technical scheme that the present invention takes is:
A kind of Chinese medicine compound for the treatment of coronary heart disease, it is made up of the raw material of following parts by weight: 6~60 parts of Radix Ophiopogonis, 3~15 parts of Fructus Corni, 3~20 parts of Hirudos, 6~60 parts of Radix Rhodiolaes, 6~60 parts of Folium Ginkgos, 6~60 parts of Rhizoma Polygoni Cuspidati.
As preferred version, the Chinese medicine compound of described treatment coronary heart disease, it is made up of the raw material of following parts by weight: 15~25 parts of Radix Ophiopogonis, 3~10 parts of Fructus Corni, 3~10 parts of Hirudos, 10~25 parts of Radix Rhodiolaes, 10~25 parts of Folium Ginkgos, 10~25 parts of Rhizoma Polygoni Cuspidati.
As preferred version, the Chinese medicine compound of described treatment coronary heart disease, it is made up of the raw material of following parts by weight: 10~60 parts of Radix Ophiopogonis, 5~15 parts of Fructus Corni, 5~20 parts of Hirudos, 10~50 parts of Radix Rhodiolaes, 10~50 parts of Folium Ginkgos, 10~50 parts of Rhizoma Polygoni Cuspidati.
As more preferably scheme, the Chinese medicine compound of described treatment coronary heart disease, it is made up of the raw material of following parts by weight: 20~50 parts of Radix Ophiopogonis, 8~15 parts of Fructus Corni, 8~20 parts of Hirudos, 15~50 parts of Radix Rhodiolaes, 15~50 parts of Folium Ginkgos, 15~50 parts of Rhizoma Polygoni Cuspidati.
As further preferred version, the Chinese medicine compound of described treatment coronary heart disease, it is made up of the raw material of following parts by weight: 40~50 parts of Radix Ophiopogonis, 10~15 parts of Fructus Corni, 10~15 parts of Hirudos, 20~40 parts of Radix Rhodiolaes, 20~40 parts of Folium Ginkgos, 20~40 parts of Rhizoma Polygoni Cuspidati.
Chinese medicine compound provided by the invention according to Chinese medical theory, adopts determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, and carries out composition of prescription according to cause of coronary heart disease mechanism, and monarch drug sweet in the mouth Radix Ophiopogonis, little hardship are slightly cold in the side.Return stomach, lung, heart channel, merit is in YIN nourishing and the production of body fluid promoting, and lung moistening clears away heart-fire, and pharmacological evaluation proves that it can significantly improve the laboratory animal hypoxia-bearing capability, increases coronary flow, and myocardial ischemia is had obvious protective effect, and can arrhythmia and improve myocardial contraction; The ministerial drug Fructus Corni is the cloudy medicine of liver and kidney tonifying in the side, and invigorating heart and kidney power is strong, and pharmacological research shows that Fructus Corni has heart tonifying, shock, antioxidation, blood fat reducing function preferably; Another ministerial drug Hirudo, salty, bitter, flat, return Liver Channel, merit is stimulated the menstrual flow at removing blood stasis, Zhu Yu Xiao Disorder, have anticoagulation and platelet aggregation, suppress thrombosis, the effect of simultaneously all right blood fat reducing, atherosclerosis, reduction blood viscosity, share with Fructus Corni, assist a ruler in governing a country the function that monarch drug is exercised nourishing yin and activating blood Radix Ophiopogonis jointly; The adjuvant drug Folium Ginkgo, sweet, bitter, puckery, GUIXIN, lung meridian have the effect of blood circulation promoting and blood stasis dispelling, TONGMAI SHULUO, and it mainly contains effective constituent is flavone compound, can blood fat reducing, blood vessel dilating, blood circulation promoting, the effect of reduction myocardial oxygen consumption; Another adjuvant drug Radix Rhodiolae, flavor is cold, sweet, puckery, return spleen, lung meridian, have QI invigorating, invigorate blood circulation, the effect of blood stasis dispelling, experimentation shows that Radix Rhodiolae can increase amount of hemoglobin, improve oxygen content, reduce the load of heart, strengthen the blood-pumping function of Ischemic Heart, accelerate blood flow, repair impaired myocardial cell, reduce the area of myocardial infarction, myocardial ischemia is had significant protective effect, Hirudo is to strengthen the power of disperse blood stasis and dredge collateral in the cooperation side; Rhizoma Polygoni Cuspidati bitter in the mouth, acid, cold nature is returned liver, gallbladder meridian, has promoting blood circulation to remove blood stasis, dispelling wind and removing obstruction in the collateral, clearing away heat-damp and promoting diuresis, the removing pathogenic heat from blood and toxic substance from the body effect studies show that Rhizoma Polygoni Cuspidati has obvious blood pressure lowering, decreased heart rate, positive inotropic action, blood fat reducing, antiinflammatory, thereby improve heart blood supply, the protection damaged myocardium improves cardiac function; And effectively prevention of arterial is atherosis.The assistant monarch drug is to strengthen the power of replenishing YIN and removing heat.It is Hirudo extract as the composition of NIAOXUEKANG commonly used that multi-flavor medicine in the prescription all has the corresponding product for the treatment of cardiovascular and cerebrovascular disease separately clinically; SHUXUENING tablet and injection are Folium Ginkgo extract; Rhodiola kirilowii Regel, Nuodikang etc. are the extracts of Radix Rhodiolae, during use effect single relatively, can not bring into play the advantage of differentiation of tcm well, we both sincerely kept " treatment must aim at the pathogenesis of disease ", and yin nourishing is with the sering that makes moist, and QI invigorating is with fortune blood, prevent to stop in the blood stasis by setting upright, promote that blood is capable; Do not forget " attacking heresy takes stopgap measures " again, heat clearing and blood circulation promoting is with disperse blood stasis and dredge collateral.Take a broad view of full side, reinforcement and elimination in combination, giving consideration to both the incidental and fundamental, tonify without causing stagnation is attacked and is not lost, and has and stress; Selected medicinal flavor is gentle, cooperatively interacts, and gives full play to the differentiation of tcm advantage, very cuts the key of coronary heart disease (CHD) pathogenesis.
Chinese medicine compound provided by the invention can become oral liquid, granule, capsule, tablet, injectable powder or injection drug form with each extracts of bulk drugs or the further purified Chinese medicine compound effective site of 80~90% precipitate with ethanol with pharmaceutically acceptable preparing carriers.
When the extract of each raw material of Chinese medicine compound provided by the invention is made oral liquid,, filter, add syrup, regulate pH value, make oral liquid the extract adding distil water dissolving of each raw material.
When the extract of each raw material of Chinese medicine compound provided by the invention is made tablet,, add magnesium stearate lubricant when needing each raw material and lactose or corn starch, mix homogeneously, granulate, tabletting is made tablet then.
When the extract of Chinese medicine compound provided by the invention is made capsule the extract of each raw material and carrier lactose or corn starch mix homogeneously, granulate, the encapsulated then capsule of making.
When the extract of each raw material of Chinese medicine compound provided by the invention is made granule, the extract of each raw material and diluent lactose or corn starch, mix homogeneously, granulate, drying is made granule.
When the extract of each raw material of Chinese medicine compound provided by the invention was made injectable powder, the extract lyophilization of each raw material, injectable powder was made in sterilization.
When the extract of each raw material of Chinese medicine compound provided by the invention is made injection, the extract of getting each raw material adds physiological saline solution and adds activated carbon then, stir, 80 ℃ were heated 30 minutes, filter, regulate pH value, be filtered to clear and bright with sintered glass funnel or other filter, fill was made injection in 30 minutes 100 to 115 ℃ of sterilizations.
The preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) gets 6~60 parts of Radix Ophiopogonis, 3~15 parts of Fructus Corni, 3~20 parts of Hirudos, 6~60 parts of Radix Rhodiolaes, 6~60 parts of Folium Ginkgos, 6~60 parts of Rhizoma Polygoni Cuspidati in proportion, earlier measuring concentration with 8~10 times of medical materials is 30~80% alcohol reflux 2~3 times, each 1~2 hour, merge extractive liquid,, concentrate, it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 60~85%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get precipitate with ethanol concentrated solution that step (2) obtains becomes oral liquid, granule, capsule, tablet, injectable powder or injection dosage form with pharmaceutically acceptable preparing carriers medicine.
Chinese medicine compound provided by the invention and the application of various preparations in preventing and treating coronary heart disease for preparing thereof.
Beneficial effect: the present invention is according to the Chinese medical theory of determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, carry out the Chinese prescription screening according to incidence of coronary heart disease mechanism, the Chinese medicine compound proportioning that provides is scientific and reasonable, medication is rigorous, and experimental result shows that Chinese medicine compound provided by the invention has good nourishing heart-disney, heat clearing and blood circulation promoting, the disperse blood stasis and dredge collateral effect, and can obviously improve the arteria coronaria blood circulation, improve myocardial ischemia; Has stronger antianginal, antithrombotic, anticoagulant improves lipid metabolism, improves the effect of the arteriosclerotic inflammation of blood vessel wall, and the extract of Chinese medicine compound provided by the invention can make things convenient for pharmaceutical carriers and is prepared into multiple dosage form, taking convenience, and experimental result clinically shows Chinese medicine compound provided by the invention, and dosage is few, safe in utilization, the life-time service toxic and side effects is little.
The specific embodiment:
Further illustrate the present invention below in conjunction with specific embodiment, should understand these embodiment only is used to the present invention is described and is not used in and limit the scope of the invention, after having read the present invention, those skilled in the art all fall within the application's claims institute restricted portion to the modification of the various equivalent form of values of the present invention.
Embodiment 1
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 20 gram, Fructus Corni 9 grams, Hirudo 10 grams, Radix Rhodiolae 15 grams, Folium Ginkgo 15 grams, Rhizoma Polygoni Cuspidati 15 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 20, Fructus Corni 8 grams, Hirudo 10 grams, Radix Rhodiolae 15 grams, Folium Ginkgo 15 grams, Rhizoma Polygoni Cuspidati 15 grams in proportion, is 60% alcohol reflux 3 times with 8 times of amounts of medical material concentration earlier, and each 1.5 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 80%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get precipitate with ethanol concentrated solution (effective site) and carrier lactose or the corn starch mix homogeneously that step (2) obtains, granulate, the encapsulated then capsule of making.(lot number: 001)
Embodiment 2
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 60 gram, Fructus Corni 15 grams, Hirudo 20 grams, Radix Rhodiolae 60 grams, Folium Ginkgo 60 grams, Rhizoma Polygoni Cuspidati 60 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 60, Fructus Corni 15 grams, Hirudo 20 grams, Radix Rhodiolae 60 grams, Folium Ginkgo 60 grams, Rhizoma Polygoni Cuspidati 60 grams in proportion, is 60% alcohol reflux 3 times with 8 times of amounts of medical material concentration earlier, and each 1.5 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 80%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get the precipitate with ethanol concentrated solution adding distil water dissolving that step (2) obtains, filter, add syrup, regulate pH value, make oral liquid.(lot number: 002)
Embodiment 3
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 50 gram, Fructus Corni 12 grams, Hirudo 15 grams, Radix Rhodiolae 50 grams, Folium Ginkgo 50 grams, Rhizoma Polygoni Cuspidati 50 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 50, Fructus Corni 10 grams, Hirudo 15 grams, Radix Rhodiolae 50 grams, Folium Ginkgo 50 grams, Rhizoma Polygoni Cuspidati 50 grams in proportion, is 50% alcohol reflux 2 times with 8 times of amounts of medical material concentration earlier, and each 2 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 80%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get precipitate with ethanol concentrated solution adding diluent cyclodextrin or the corn starch mix homogeneously that step (2) obtains, granulate, drying is made granule.(lot number: 003)
Embodiment 4
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 30 gram, Fructus Corni 10 grams, Hirudo 10 grams, Radix Rhodiolae 15 grams, Folium Ginkgo 15 grams, Rhizoma Polygoni Cuspidati 15 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 30, Fructus Corni 8 grams, Hirudo 10 grams, Radix Rhodiolae 15 grams, Folium Ginkgo 15 grams, Rhizoma Polygoni Cuspidati 15 grams in proportion, is 40% alcohol reflux 2 times with 10 times of amounts of medical material concentration earlier, and each 2 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 80%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get the precipitate with ethanol concentrated solution lyophilization that step (2) obtains, injectable powder is made in sterilization.(lot number: 004)
Embodiment 5
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 40 gram, Fructus Corni 12 grams, Hirudo 10 grams, Radix Rhodiolae 20 grams, Folium Ginkgo 20 grams, Rhizoma Polygoni Cuspidati 20 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 40, Fructus Corni 10 grams, Hirudo 10 grams, Radix Rhodiolae 20 grams, Folium Ginkgo 20 grams, Rhizoma Polygoni Cuspidati 20 grams in proportion, is 60% alcohol reflux 2 times with 8 times of amounts of medical material concentration earlier, and each 2 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 85%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get the precipitate with ethanol concentrated solution adding cyclodextrin mix homogeneously that step (2) obtains, add magnesium stearate lubricant, mix homogeneously, granulate, tabletting is made tablet then.(lot number: 005)
Embodiment 6
1, the Chinese medicine compound crude drug is formed: Radix Ophiopogonis 60 gram, Fructus Corni 10 grams, Hirudo 10 grams, Radix Rhodiolae 30 grams, Folium Ginkgo 30 grams, Rhizoma Polygoni Cuspidati 30 grams.
2, the preparation method of compound Chinese medicinal preparation provided by the invention may further comprise the steps:
(1) getting gram Radix Ophiopogonis 60, Fructus Corni 10 grams, Hirudo 10 grams, Radix Rhodiolae 30 grams, Folium Ginkgo 30 grams, Rhizoma Polygoni Cuspidati 30 grams in proportion, is 70% alcohol reflux 2 times with 8 times of amounts of medical material concentration earlier, and each 2 hours, merge extractive liquid, concentrated, and it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 85%, leave standstill, precipitation is got supernatant, concentrates, and gets precipitate with ethanol concentrated solution (effective site), and is standby;
(3) get the precipitate with ethanol concentrated solution adding cyclodextrin mix homogeneously that step (2) obtains, add magnesium stearate lubricant, mix homogeneously, granulate, tabletting is made tablet then.(lot number: 006)
Embodiment 7 Chinese medicine compound are to the influence of rat experiment myocardial ischemia
1, experiment material
1.1 be subjected to the reagent thing: Chinese medicine compound provided by the invention (lot number: 001); The control drug compound Salviae Miltiorrhizae: Shanghai first pharmaceutical factory produces; Pituitrin, the biochemical-pharmaceutical factory, Shanghai provides; Superoxide dismutase (SOD), malonaldehyde (MDA), creatine phosphokinase (CPK) test kit, Nanjing is built up bio-engineering research and is provided; Chlorination nitro four nitrogen blue (NBI), the Shanghai chemical reagent work that advances produces.
1.2 laboratory animal: the SD rat is provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.
1.3 instrument LMS-ZB type two is led physiograph, Chengdu Instruement Factory produces, the DH-140 artificial ventilator, and Zhejiang Medical university instrument experiment factory produces; 722 type spectrophotometers, analytical tool factory in Shanghai produces; JN-A type precision torsion balance, Shanghai Second Balance Factory produces.
2, experimental technique and result
2.1 40 of SD rats are got in the influence to Acute Myocardial Ischemia in Rats due to the pituitrin, male and female half and half, body weight 180~220 grams, be divided into model group, compound Salviae Miltiorrhizae group 2g/kg at random, Chinese medicine compound high concentration group 43g/kg, low concentration group 17.2g/kg, every group of 10 mouse.Little, heavy dose of group gastric infusion every day of compound Salviae Miltiorrhizae group and Chinese medicine compound 1 time, model group is given the normal saline with the capacity of grade, continuous 10 days.1h after the last administration, record mark I lead electrocardiogram, by Sublingual iv pituitrin lu/kg, capacity is Iml/kg, finish in the 15S injection, the electrocardiogram of tracing 5S, 15S, 30S, 1min, 2min, 3min and 5min then immediately changes, and measures and relatively gives the variation that the ST section is raised of pituitrin front and back, with t check carrying out statistical analysis between group.Concrete experimental result is shown in Table 1.
Table 1 Chinese medicine compound and compound Salviae Miltiorrhizae cause the influence that rat heart muscle sum of ischemia ST section moves to pituitrin
Figure BSA00000180734600061
Compare with model group *P<0.05, *P<0.01
Show that by table 1 experimental result Chinese medicine compound provided by the invention can effectively reduce rat heart muscle sum of ischemia ST section moves, and show that Chinese medicine compound provided by the invention has good improvement and protective effect to myocardial ischemia, and effect is better than the compound Salviae Miltiorrhizae group.
2.2 to the rat myocardium block scope, the influence of SOD in serum, MDA and CPK
Get 40 of SD rats, male and female half and half, body weight 250~300g is divided into model group, ligation group, compound Salviae Miltiorrhizae group 2g/kg at random, Chinese medicine compound high concentration group 43g/kg, low concentration group 17.2g/kg, every group of 10 mouse.Each group is opened breast with pentobarbital sodium 30mg/kg ip anesthesia through the parasternal approach for cardiac surgery stringer, practices artificial respiration immediately, expose behind the heart with No. 0 silk thread ligation left coronary artery anterior descending branch, to cause myocardial ischemia (the not ligation of pseudo-ligation group), close the thoracic cavity then, skin suture.Postoperative, except that pseudo-ligation group and model group, all the other group gastric infusions every day 1 time, successive administration 10 days, behind the last administration 30min, carotid artery is got blood, the content of SOD, MDA and CPK in the mensuration serum.Win heart, inhale the branch that anhydrates, claim heavy whole-heartedly with filter paper.Cut off the atrium, the ventricle crosscut is become 4, place the 0.5%NBT phosphate buffer of pH value 7.4, the 15min that dyes in 37 ℃ of calorstats isolates infarcted myocardium and weighs, and calculates infarcted myocardium and accounts for the percent of weight in wet base (being myocardial infarct size) whole-heartedly.Concrete experimental result is as shown in table 2.
Table 2 Chinese medicine compound is to the influence of rat blood serum SOD, MDA, CPK and infarction size
Group Dosage (g/kg) ??SOD(Nu/ml) ??MDA??(nmol/ml) ??CPK??(u/ml) Heart infarction district/heart
Model group ??-- ??181.45±89.25 ??289.12±39.27 ??37.58±5.85 ??28.19±2.12
Ligation group ??-- ??378.28±95.14 ??135.28±29.36 ??13.58±3.78 ??5.27±1.28
The compound Salviae Miltiorrhizae group ??2 ??238.18±35.27 ??253.58±59.36 ??27.59±6.58 ??28.18±2.58
The Chinese medicine compound low dose group ??17.2 ??451.78±38.048 ** ??101.48±31.78 * ??11.28±3.12 ** ??11.28±1.21 **
The Chinese medicine compound high dose group ??34.4 ??473.14±40.72 ** ??90.28±45.28 * ??8.08±1.28 ** ??9.27±1.29 **
Compare with model group *P<0.05, *P<0.01
Experimental result by table 2 shows that Chinese medicine compound provided by the invention can obviously be dwindled the myocardial infarct size of coronary ligation rat.When cardiac muscle generation hypoxic-ischemic, respective change also takes place in the biochemical metabolism aspect thereupon, free-radical generating increases, oxidation resistance descends in the tissue, lipid peroxidation takes place in the polyunsaturated fatty acids reaction on oxygen-derived free radicals and the cell membrane, its peroxidating product malonaldehyde (MDA) has very strong destruction to film, continuous injury of myocardium form and contain the protein and the enzyme of sulfenyl, cause calcium overload, and then inhibition cardiac function, finally cause myocardial cell from the reversibility lesion development to irreversible damage, until cell death.This result of study shows; the Chinese medicine compound SOD vigor in the serum that can raise; thereby strengthened the function of endogenous oxygen radical removing system; thereby can reduce the generation of MDA; release to CPK also has obvious inhibitory action; can dwindle myocardial infarct size, prove that Chinese medicine compound provided by the invention has significant protective effect to myocardial ischemia.
Embodiment 8 Chinese medicine compound are to the influence of hyperlipidemia rats
1, experiment material: Chinese medicine compound (lot number: 004); Evening Primrose Oil, Xiamen Cod-liver Oil Factory produces; Serum total cholesterol test kit, serum triglycerides test kit, low-density lipoprotein cholesterol test kit, HDL-C test kit are produced by the glad biotechnology research of Shanghai section; 40 of SD rats, male and female half and half, body weight 140~160g is provided by Nanjing University of Traditional Chinese Medicine's Experimental Animal Center.Instrument: the vital200 automatic clinical chemistry analyzer, Dutch prestige figure scientific instrument company produces.R80 type automatic blood flow graph, Beijing Steellex Scientific Instrument Company produces.
2, experimental technique
40 of SD rats eat the adaptability feedstuff after 1 week, fasting (can't help water) 12h, and eye socket is got blood, surveys serum cholesterol (TC), and triglyceride (TG) is grouped into: the normal control group; Model group; Radix Oenotherae erythrosepalae oil positive controls administration every day 0.6g/kg; Chinese medicine compound small dose group administration every day 17.2g/kg; The heavy dose of group of Chinese medicine compound administration every day 34.4g/kg, sub-cage rearing.Matched group is fed normal diet, and all the other groups are fed high lipid foods, 2.0% cholesterol of filling a prescription, 10% Adeps Sus domestica, 0.1% methylthiouracil, 0.25 sodium cholate, 87.7% normal feedstuff: every day every feeding 20g, after waiting to eat up, add normal feedstuff again.When giving high lipid food, each group gives the medicine of above-mentioned dosage, and matched group and model group are given distilled water, all adopts per os to irritate stomach, and capacity is 1ml/100g, every day 1 time, continuous 8 weeks.After administration 4 week and 8 weeks, drug withdrawal, respectively surveyed the rat fat level in 10 days.Last carotid artery is got blood, does blood examination.
3, experimental result
4 week of administration, model group was found in the back, and TC, TG, LDL-C show the hyperlipidemia model success apparently higher than the normal control group, big low dose of Chinese medicine compound and Radix Oenotherae erythrosepalae oil all can reduce blood significantly, TC, TG, LDL-C, and the HDL-C that raises significantly relatively have significant difference with model group.Big low dose of Chinese medicine compound and Radix Oenotherae erythrosepalae oil all can reduce blood TC, TG, LDL-C significantly after 8 weeks of administration, and the HDL-C that raises significantly, with the model group comparing difference significance are arranged.And heavy dose is organized and the Radix Oenotherae erythrosepalae line of oils relatively raises, and the HDL-C effect is more remarkable.10 days big small dose group of Chinese medicine compound and the Radix Oenotherae erythrosepalae line of oils difference of comparing with model group still has significance after the drug withdrawal, and heavy dose ofly relatively reduces the LDL-C effect significantly with the Radix Oenotherae erythrosepalae line of oils.8 weeks of administration, hyperlipemia model detects the hemorheology of rat index after setting up simultaneously, and model group whole blood viscosity, blood plasma viscosity all are higher than normal group, and each index of Chinese medicine compound size agent group all significantly is lower than model group, and effect is better than Radix Oenotherae erythrosepalae oil, and concrete experimental result is as shown in table 3.Show that by above experimental result Chinese medicine compound can regulate lipid metabolism: 1, can obviously reduce hyperlipidemia rats blood TC, TG, LDL-C level, improve hyperlipemia, the atherosis formation of prevention of arterial, the HDL-C level that can raise significantly again stops development of atherosclerosis; 2, protection endotheliocyte by transferring the protection of fat and antioxidation dual function, reduces lipidosis, the formation of prevention of arterial sclerosis pathological changes; 3, can obviously reduce whole blood viscosity and blood plasma viscosity, thereby prevent that effectively blood is in high glutinous, hypercoagulability, improves hemorheology.
TC, TG, LDL-C, HDL-C and the blood plasma k value of each experimental group after 8 weeks of table 3 administration
Figure BSA00000180734600081
Group Number of animals (n) ??TC??(mmol/l) ??TG??(mmol/l) ??HDL-C??(mmol/l) ??LDL-C??(mmol/l) Blood plasma viscosity (mPa/s)
The normal control group ??8 ??1.83±0.28 ??1.84±0.31 ??1.51±0.21 ??1.78±0.31 ??1.12±0.21
The hyperlipidemia model group ??8 ??6.57±1.46 ??5.08±0.27 ??0.18±0.09 ??3.08±0.89 ??2.05±0.57
The Radix Oenotherae erythrosepalae line of oils ??8 ??2.01±0.41 ??1.68±0.18 * ??0.37±0.11 ??1.98±0.28 * ??1.45±0.38 **
The Chinese medicine compound low dose group ??8 ??1.65±0.31 ** ??1.61±0.14 * ??0.68±0.12?? ** ??1.58±0.31?? ** ??1.12±0.21 **
The Chinese medicine compound high dose group ??8 ??1.38±0.28 ** ??1.28±0.21?? ** ??0.84±0.13?? ** ??1.28±0.18?? ** ??0.98±0.17 **
The clinical research of embodiment 8 compound of Chinese medicine coronary heart disease
1, clinical data
Selection meets International Society of Cardiology and association and World Health Organization's clinical name diagnostic standardization associating special topic group report " name of ischemic heart desease and diagnostic criteria ", and meet patients with coronary heart disease 63 examples that traditional Chinese medical science heart deficiency of the kidney yin stasis of blood resistance venation is demonstrate,proved the dialectical standard Chinese medical discrimination standard of angina pectoris (in " the new Chinese medicine clinical research guideline " developed and published with reference to health ministry in 1993 about), inpatient's 51 examples wherein, outpatient's 12 examples are divided into treatment group 33 example and matched group 30 examples at random.Wherein male 20 examples are organized in treatment, women 13 examples, 46~73 years old age, average (60.3 ± 8.7) year, the course of disease 1~20 year, average (9.0 ± 3.3) year; Matched group man 16 examples, women 14 examples, 43~70 years old age, average (59.7 ± 9.0) year, the course of disease 1~20 year, average (8.9 ± 2.5) year.The angina pectoris attacks degree: the treatment group, slight 20 examples, moderate 1 example is than severe 3 examples; Matched group, slight 11 examples, moderate 9 examples are than severe 1 example.Doctor trained in Western medicine typing: treatment group, stable type 33 examples, instability mode 9 examples; Matched group, stable type 17 examples, instability mode 4 examples.At aspects such as sex, age, the course of disease, angina pectoris attacks degree and typings, the difference (P>0.05) of learn handling by statistics that there are no significant has comparability between 2 groups of patients.
2, Therapeutic Method and observation index
2.1 Therapeutic Method
Treatment group: Chinese medicine compound granule provided by the invention, oral each 2 bags (whenever comprising crude drug 37.5g), every day 2 times.Matched group: the coronary disease still, Baoding herbal pharmaceutical responsibility company limited is produced, and is oral, and each 4, every day 3 times.More than 2 groups observe case and be for 4 weeks the course of treatment.The medicine of withdrawing all antianginals, blood fat reducing before the administration and influencing biologically active pdgf is more than 1 week.If angina pectoris can not be controlled to withdraw and truly have difficult person to give the nitroglycerin sublingual administration.2 groups of cases no longer add other similar Chinese and western drugses in duration of test except that nitroglycerin.
2.2 observation index
(1) variation of angina pectoris attacks: observe angina pectoris attacks time, degree, number of times, persistent period, induced factor.
(2) electrocardiogram changes before and after the treatment.
(3) blood fat and lipoprotein (α): this experiment is with enzymatic assays plasma cholesterol (TC), triglyceride (TG), HDL-C (HDL-C), try to achieve low-density lipoprotein cholesterol (LDL-C) by the Friedewald formula, measure plasma lipoprotein (α) [Lp (α)] with euzymelinked immunosorbent assay (ELISA).Platelet α granule Trypsin (GMP-140), platelet maximum agglutination rate (PAGM), D-dimer (D-D): put the method for exempting from double antibodies sandwich and measure GMP-140, medicine box is provided by Suzhou Medical College thrombosis chamber; With the SPA-4 type function platelet aggregation instrument that Shanghai Kodak instrument test company produces, press turbidimetry for Determination PAGM; Detect D-D with enzyme labeled immunoassay adsorption analysis method, test kit is provided by Shanghai pupil's thing technology company of fighting.The project of below respectively stating is measured when the beginning administration and after the end administration respectively.
3, therapeutic outcome
Criterion of therapeutical effect is carried out with reference to therapy of combining Chinese and Western medicine angina pectoris in 1979 and arrhythmia forum " angina pectoris and ECG curative effect criterion ".
3.1 antianginal result: concrete experimental result is as shown in table 4:
Table 4 antianginal curative effect
Group The example number Produce effects Effectively Invalid Increase the weight of Obvious effective rate (%) Total effective rate (%)
The Chinese medicine compound group ??33 ??25 ??7 ??1 ??0 ??75.75 ??96.96%
Matched group ??30 ??10 ??6 ??12 ??2 ??33.33 ??53.33
As shown in Table 4, Chinese medicine compound provided by the invention has obvious antianginal effect, compares with matched group, and the antianginal total effective rate and the obvious effective rate of Chinese medicine compound group all are higher than matched group, and 2 groups relatively have significant difference.
3.2 ECG curative effect: concrete experimental result is as shown in table 5:
Table 5 ECG curative effect
Group The example number Produce effects Effectively Invalid Increase the weight of Obvious effective rate (%) Total effective rate (%)
The Chinese medicine compound group ??33 ??15 ??10 ??8 ??0 ??45.45 ??75.75
Matched group ??30 ??4 ??6 ??15 ??5 ??13.33 ??33.33
As shown in Table 5, Chinese medicine compound provided by the invention can effectively be improved electrocardiogram, and effect is better than matched group, proves that further Chinese medicine compound provided by the invention has antianginal effect preferably.
3.3 the influence to blood coagulation and fibrinolytic system: measure after the administration and respectively organize platelet α granule Trypsin (GMP-140), platelet maximum agglutination rate (PAGM), D-dimer (D-D) value, concrete experimental result is as shown in table 6:
The influence of table 6 pair blood coagulation and fibrinolytic system
Figure BSA00000180734600101
It is relatively preceding with treatment, *P<0.05, *P<0.01
Experimental result by table 6 shows, Chinese medicine compound provided by the invention can significantly reduce platelet α granule Trypsin (GMP-140) and D-dimer (D-D) value among the coronary heart disease patients serum, and can reduce platelet maximum agglutination rate (PAGM), illustrate that Chinese medicine compound provided by the invention can obviously improve hemorheology, have good anticoagulant, antithrombotic effect, can be used to prevent and treat coronary heart disease.
The present invention is according to Chinese medical theory, adopt the theory of determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs, and carry out the proportioning prescription according to cause of coronary heart disease mechanism, show by above experimental result, Chinese medicine compound provided by the invention has good nourishing heart-disney, heat clearing and blood circulation promoting, disperse blood stasis and dredge collateral effect, and can obviously improve the arteria coronaria blood circulation, improve myocardial ischemia; Have stronger antianginal, antithrombotic, anticoagulant, blood fat reducing improves the effect of lipid metabolism.And do not see untoward reaction in the experimentation, medication is safer.
The above only is a preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (8)

1. a Chinese medicine compound for the treatment of coronary heart disease is characterized in that, it is made up of the raw material of following parts by weight: 6~60 parts of Radix Ophiopogonis, 3~15 parts of Fructus Corni, 3~20 parts of Hirudos, 6~60 parts of Radix Rhodiolaes, 6~60 parts of Folium Ginkgos, 6~60 parts of Rhizoma Polygoni Cuspidati.
2. the Chinese medicine compound of treatment coronary heart disease according to claim 1, it is characterized in that it is made up of the raw material of following parts by weight: 15~25 parts of Radix Ophiopogonis, 3~10 parts of Fructus Corni, 3~10 parts of Hirudos, 10~25 parts of Radix Rhodiolaes, 10~25 parts of Folium Ginkgos, 10~25 parts of Rhizoma Polygoni Cuspidati.
3. the Chinese medicine compound of treatment coronary heart disease according to claim 1, it is characterized in that it is made up of the raw material of following parts by weight: 10~60 parts of Radix Ophiopogonis, 5~15 parts of Fructus Corni, 5~20 parts of Hirudos, 10~50 parts of Radix Rhodiolaes, 10~50 parts of Folium Ginkgos, 10~50 parts of Rhizoma Polygoni Cuspidati.
4. the Chinese medicine compound of treatment coronary heart disease according to claim 3, it is characterized in that it is made up of the raw material of following parts by weight: 20~50 parts of Radix Ophiopogonis, 8~15 parts of Fructus Corni, 8~20 parts of Hirudos, 15~50 parts of Radix Rhodiolaes, 15~50 parts of Folium Ginkgos, 15~50 parts of Rhizoma Polygoni Cuspidati.
5. the Chinese medicine compound of treatment coronary heart disease according to claim 4, it is characterized in that it is made up of the raw material of following parts by weight: 40~50 parts of Radix Ophiopogonis, 10~15 parts of Fructus Corni, 10~15 parts of Hirudos, 20~40 parts of Radix Rhodiolaes, 20~40 parts of Folium Ginkgos, 20~40 parts of Rhizoma Polygoni Cuspidati.
6. the Chinese medicine compound of each described treatment coronary heart disease of claim 1 to 5, it is characterized in that, each raw extract is become the medicine of oral liquid, granule, capsule, tablet, injectable powder, drop pill, soft capsule or injection dosage form with pharmaceutically acceptable preparing carriers.
7. the preparation method of the Chinese medicine compound of the described treatment coronary heart disease of claim 6 is characterized in that may further comprise the steps:
(1) gets 6~60 parts of Radix Ophiopogonis, 3~15 parts of Fructus Corni, 3~20 parts of Hirudos, 6~60 parts of Radix Rhodiolaes, 6~60 parts of Folium Ginkgos, 6~60 parts of Rhizoma Polygoni Cuspidati by the described parts by weight of claim 1, earlier measuring concentration with 8~10 times of medical materials is 30~80% alcohol reflux 2~3 times, each 1~2 hour, merge extractive liquid,, concentrate, it is standby to get concentrated solution;
(2) get the concentrated solution that step (1) obtains, add ethanol, make concentration of ethanol reach 60~85%, leave standstill, precipitation is got supernatant, concentrates, and gets the precipitate with ethanol concentrated solution, and promptly effective site is standby;
(3) get effective site that step (2) obtains becomes oral liquid, granule, capsule, tablet, injectable powder, drop pill, soft capsule or injection dosage form with pharmaceutically acceptable preparing carriers medicine.
8. the application of each described Chinese medicine compound of claim 1 to 5 in preparation treatment medicaments for coronary disease.
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109837A (en) * 2016-08-26 2016-11-16 张泽钧 A kind of Chinese medicine treating coronary heart disease
CN106581579A (en) * 2016-12-12 2017-04-26 西安医学院 Chinese herbal medicinal composition for treating coronary heart disease and preparation method of Chinese herbal medicinal composition
CN107243023A (en) * 2017-06-23 2017-10-13 云南省中医医院 It is a kind of to treat Chinese medicine composition of hyperlipemia and preparation method thereof and instructions of taking
CN108743800A (en) * 2018-09-13 2018-11-06 百色市右江区兆石投资咨询策划服务部 A kind of traditional Chinese medicine powder for treating cardiovascular and cerebrovascular

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Publication number Priority date Publication date Assignee Title
CN101214314A (en) * 2008-01-18 2008-07-09 张建洋 Chinese medicine for treating cerebral apoplexy

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
CN101214314A (en) * 2008-01-18 2008-07-09 张建洋 Chinese medicine for treating cerebral apoplexy

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106109837A (en) * 2016-08-26 2016-11-16 张泽钧 A kind of Chinese medicine treating coronary heart disease
CN106581579A (en) * 2016-12-12 2017-04-26 西安医学院 Chinese herbal medicinal composition for treating coronary heart disease and preparation method of Chinese herbal medicinal composition
CN107243023A (en) * 2017-06-23 2017-10-13 云南省中医医院 It is a kind of to treat Chinese medicine composition of hyperlipemia and preparation method thereof and instructions of taking
CN108743800A (en) * 2018-09-13 2018-11-06 百色市右江区兆石投资咨询策划服务部 A kind of traditional Chinese medicine powder for treating cardiovascular and cerebrovascular

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